Rv1073 Family assigned · low

H37Rv Rv1073 · MTBC0 mtbc0_001153 · 283 aa · 1205500–1206351 (+) · RefSeq NP_215589.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Nicking-endonuclease-like fold (type-II nicking enzyme V.NaeI-like). RefSeq leaves it 'hypothetical protein'.

Curated reference (UniProt)

UniProt O53421 TrEMBL · unreviewed · Predicted
UniProt nameCullin, a subunit of E3 ubiquitin ligase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein conserved in bacteria
Orthologous groupCOG2852

Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.

Conservation & selection (intra-MTBC, 145 209 strains)

pN/pS 0.658 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 2 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.21% of strains (307) · clonal

pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.

Domains (Pfam, hmmscan --cut_ga)

No Pfam-A domain above the gathering threshold (or not yet scanned).

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 96.3 (very high). A confident model makes the fold comparison meaningful.

Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.

TargetProbTME-valueDescription
3r3p-assembly1_B 1.00 0.72 8.3e-02 3r3p-assembly1_B Homing Endonuclease I-Bth0305I Catalytic Domain
9g6k-assembly1_L9 0.66 0.37 8.8e-02 9g6k-assembly1_L9 LSU structure derived from the LSU sample of the mitoribosome from T. gondii.
6z1p-assembly1_AS 0.35 0.32 1.3e-01 6z1p-assembly1_AS Structure of the mitochondrial ribosome from Tetrahymena thermophila
8bao-assembly1_B 0.33 0.48 1.1e+00 8bao-assembly1_B Dysgonamonadaceae bacterium CRISPR ancillary nuclease 2
2inb-assembly1_A-2 0.20 0.44 9.5e-01 2inb-assembly1_A-2 Crystal structure of an XisH family protein (ZP_00107633.1) from Nostoc punctiforme PCC 73102 at 1.60 A resolution
8b6h-assembly1_EJ 0.18 0.40 8.4e-01 8b6h-assembly1_EJ Cryo-EM structure of cytochrome c oxidase dimer (complex IV) from respiratory supercomplex of Tetrahymena thermophila
7yzm-assembly1_B 0.16 0.60 3.7e+00 7yzm-assembly1_B MgADPNP-bound DCCP:DCCP-R complex
7c2f-assembly2_D 0.15 0.49 3.1e+00 7c2f-assembly2_D Crystal Structure of the Thorarchaeota ProGel/rabbit actin complex

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: Rv1072 (transmembrane protein), medium confidence from genomic context alone (score 596 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2744c 35kd_ag hyp hypothetical protein 687 687 coexpression:687
Rv2100 hyp hypothetical protein 651 651 ctx cooccurence:647
Rv3776 hyp hypothetical protein 648 648 ctx cooccurence:644
Rv1072 transmembrane protein 596 596 ctx neighborhood:578
Rv0393 hyp hypothetical protein 537 537 ctx cooccurence:535
Rv3859c gltB glutamate synthase large subunit 526 527 coexpression:520
Rv0767c HTH-type transcriptional regulator 526 526 ctx cooccurence:524
Rv0336 hyp hypothetical protein 493 493 ctx cooccurence:483
Rv0515 hyp hypothetical protein 493 493 ctx cooccurence:484
Rv3810 pirG cell surface protein 492 492 ctx cooccurence:489
Rv2345 transmembrane protein 460 461 ctx cooccurence:459
Rv3707c hyp hypothetical protein 437 438 ctx cooccurence:436
Rv0320 hyp hypothetical protein 433 433 ctx cooccurence:433
Rv3668c protease 429 429 ctx cooccurence:420
Rv0169 mce1A Mce family protein Mce1A 420 420

STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.

Evidence

  • Foldseek vs AFDB-SwissProt: type II nicking enzyme V.NaeI, TM 0.55, E 1e-3
  • Structural homology vs AlphaFold-Swiss-Prot (Foldseek; 542k curated SwissProt structures), project 'Still unknown gene function' phase13, 2026-06-10. Fold/family-level, not a demonstrated function.

Sources

  • Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
  • Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_215589.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
  • Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021, doi:10.1093/molbev/msab293), eggNOG 5.0 DB (Huerta-Cepas et al. 2019) — OG COG2852
  • Curated reference: UniProt O53421 (TrEMBL, unreviewed; Predicted)
  • Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
  • Model confidence: ESMFold per-residue pLDDT (mean 96.3, very high)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 20 functional partner(s); context anchor Rv1072
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001153|Rv1073|
MGAQPFIGSEALAAGLISWHELGKYYTAIMPNVYLDKRLKPSLRQRVIAAWLWSGRKGVIAGASASALHGAKWVDDHALVELIWRNARAPNGVRTKDELLLDGEVQRLCGLTVTTVERTAFDLGRRPPLGQAITRLDALANATDFKINDVRELARKHPHTRGLRQLDKALDLVDPGAQSPKETWLRLLLINAGFPRPSTQIPLLGVYGHPKYFLDMGWEDIMLAVEYDGEQHRLSRDQFVKDVERLEYIRRAGWTHIRVLADHKGPDVVRRVRQAWDTLTSRR